Biliary clearance of erythritol is being widely used as an estimate of canalicular bile flow although review of the data upon which this use is based indicates that the data are both sparse and indirect. The validity of using erythritol clearance will be assessed more extensively in a series of indirect studies carried out in experimental animals. A direct assessment of duct permeability and function has been initiated. Basically, a major effort will be made to establish the techniques of microdissection and microperfusion of the biliary duct system as a means of directly assessing duct functions. We have devoted a considerable effort to an examination of the importance of conjugation for hepatic transport of compounds into bile. We have developed synthetic and analytical techniques that permitted an appraisal of the importance of conjugation for BSP transport in adult and neonatal guinea pigs, and adult rats. These observations are being extended in a study of dogs and non-human primates. Moreover, we plan to examine the importance of conjugation for transport of a variety of compounds excreted as glucuronides. We have initiated and plan to continue studies concerned with the possibility that phenobarbital administration will prevent and correct the impairment of hepatic excretory function induced in experimental animals by steroids such as estradiol and 17 alpha ethyl 19 nor testosterone.